Aspects of functional constipation - a trial of an opioid antagonist as a treatment and an investigation of the colonic microbiota associated with the illness

Bignell, Mark (2014) Aspects of functional constipation - a trial of an opioid antagonist as a treatment and an investigation of the colonic microbiota associated with the illness. Doctoral thesis, University of East Anglia.

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Abstract

INTRODUCTION
Functional constipation (FC) is a common condition which affects patients’ quality of life (QoL), is of uncertain pathophysiology, and is poorly treated. The aims of this research were to conduct a randomised, placebo-controlled trial investigating an opiate antagonist (Naloxone - Nalcol™) on symptom relief in FC and secondly to describe the colonic microbiota in FC and determine the effect of Nalcol™ on it.
MATERIAL AND METHODS
The trial consisted of; a 2 week screening period (Period I), a 4 week trial period of Nalcol™ vs. Placebo (Period II), and a 4 week open label period with all patients taking Nalcol™ (Period III). The primary outcome was patients’ assessment of ‘satisfactory improvement in the preceding 2 weeks’ after each period. The secondary outcomes were: changes in QoL, stool type and frequency, and transit time. A subset of patients donated stool samples at the end of each period for microbiological analysis which were compared with controls without FC. Faecal samples were analysed using denaturing gradient gel electrophoresis (DGGE), fluorescence in situ hybridisation (FISH), and pyrosequencing.
RESULTS
41 females were recruited (median age 45, range 23-76 years) .There were no significant differences in
‘satisfactory improvement in the preceding 2 weeks’, (Nalcol™ vs. Placebo, 20% vs. 24%, p=1.00, n=41) or
any secondary outcomes. Nalcol™ use was associated with more bloating (40% vs. 5%, p=0.009). Patients with FC had significant reductions in the Firmicutes phylum (25% vs. 45%, p=0.004) and Bifidiobacteria spp. (0.67 vs. 0.88 log10 cell/g, p=0.03), with increases in the Bacteroidetes phylum (66% vs. 41%, p=0.002) compared to controls.
CONCLUSION
Nalcol™ had no clinical benefits for managing FC in this trial and cannot be recommended in this group of patients. Differences in the colonic microbiota in FC warrant further investigation to see how it is implicated in the pathophysiology of FC.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Brian Watkins
Date Deposited: 14 Sep 2015 13:28
Last Modified: 14 Sep 2015 13:28
URI: https://ueaeprints.uea.ac.uk/id/eprint/54337
DOI:

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